Simvastatin: Difference between revisions
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< | <StructureSection load='' size='340' side='right' caption='Simvastatin, also known as Zocor' scene='Simvastatin/Just_simva/1'> | ||
===Better Known as: Zocor=== | ===Better Known as: Zocor=== | ||
* Marketed By: Merck & Co. Inc.<br /> | * Marketed By: Merck & Co. Inc.<br /> | ||
* Major Indication: Hyperlipidemia & High Cholesterol (Hypercholesterolemia)<br /> | * Major Indication: Hyperlipidemia & High Cholesterol ([[Metabolic Disorders|Hypercholesterolemia]])<br /> | ||
* Drug Class: [[HMGR]] Inhibitor or Statin | * Drug Class: [[HMGR]] Inhibitor or Statin | ||
* Date of FDA Approval (Patent Expiration): 1997 (2006)<br /> | * Date of FDA Approval (Patent Expiration): 1997 (2006)<br /> | ||
* 2005 Sales: $4.4 Billion <ref>http://money.cnn.com/2006/06/23/news/companies/zoloft_zocor/index.htm</ref> | * 2005 Sales: $4.4 Billion <ref>http://money.cnn.com/2006/06/23/news/companies/zoloft_zocor/index.htm</ref> | ||
* | * Importance: Zocor is one of the best selling drugs of all time and was the second best selling drug in 2005 before going off patent. Since statins are so ubiquitous, doctors have even suggested handing them out with fast food. See: [http://www.bbc.co.uk/news/health-10955522 the article] <br /> | ||
* | * See [[Pharmaceutical Drugs]] for more information about other drugs and disorders | ||
===Mechanism of Action=== | ===Mechanism of Action=== | ||
Simvastatin is rapidly hydrolyzed ''in vivo'' to generate mevinolinic acid, a powerful inhibitor of [[HMG-CoA Reductase]] (HMGR). HMGR is a <scene name='Simvastatin/Just_simva_hmg/1'>highly regulated enzyme</scene> responsible for the committed step in cholesterol synthesis. Simvastatin, like other statins, <scene name='Simvastatin/Statin_simva/1'>binds HMGR</scene> via a number of polar interactions with the "cis loop" of HMGR, particularly residues Ser 684, Asp 690, Lys 691, Lys 692, and hydrogen bond interactions between Glu 559 and Asp 767 with the O5-hydroxyl of the statins. Van der Waals interactions between Leu 562, Val 683, Leu 853, Ala 856, and Leu 857 of HMGR and hydrophobic ring structures of Simvastatin help form the pocket the drug is positioned in.<ref>PMID:11349148</ref> These interactions help Simvastatin outcompete HMG-CoA, the substrate of HMGR, in binding to HMGR.<ref>PMID:7784310</ref> | |||
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===Pharmacokinetics=== | ===Pharmacokinetics=== | ||
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{{:Statin Pharmacokinetics}} | |||
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===Effectiveness and Side Effects=== | ===Effectiveness and Side Effects=== | ||
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The Statins are one of the safest drug classes to reach block buster status. Typical adverse events include muscle weakness, headache dizziness and slightly increased creatinine kinase (CK) levels (an indication of kidney and smooth muscle damage), although these are common to all the statins (with the exception of elevated CK levels which only occurs in [[Atorvastatin]], [[Rosuvastatin]], and Simvastatin)<ref>PMID:20456733</ref> In March, 2010, the FDA issued a warning about an increased rate of Rhabdomyolysis, a dangerous breakdown of muscle fiber, releasing [[myoglobin]] into the bloodstream, potentially resulting in severe kidney damage. Although these concerns are not enough to have patients cease use of Zocor, it is important for the public to be aware of the issue. <ref>http://www.reuters.com/article/idUSTRE62I3YW20100319</ref> | The Statins are one of the safest drug classes to reach block buster status. Typical adverse events include muscle weakness, headache dizziness and slightly increased creatinine kinase (CK) levels (an indication of kidney and smooth muscle damage), although these are common to all the statins (with the exception of elevated CK levels which only occurs in [[Atorvastatin]], [[Rosuvastatin]], and Simvastatin)<ref>PMID:20456733</ref> In March, 2010, the FDA issued a warning about an increased rate of Rhabdomyolysis, a dangerous breakdown of muscle fiber, releasing [[myoglobin]] into the bloodstream, potentially resulting in severe kidney damage. Although these concerns are not enough to have patients cease use of Zocor, it is important for the public to be aware of the issue. <ref>http://www.reuters.com/article/idUSTRE62I3YW20100319</ref> | ||
===Interesting Facts=== | ===Interesting Facts=== | ||
* As with other statins which are metabolized by the CYP3A4 liver enzyme, the pharmacokinetics of Simvastatin are altered significantly by consumption of grapefruit juice. C<sub>max</sub> values of Simvastatin (40mg doses) increased by nearly 300%, t<sub>max</sub> increased 100%,, the half life decreased by 50%, and AUC increased by nearly 300%. These results are even more pronounced for active Simvastatin metabolites. <ref>DOI: 10.1111/j.1365-2125.2004.02095.x</ref> | |||
* Simvastatin is simply the methyalted form of [[Lovastatin]] an earlier Statin developed by Merck. | |||
===The Jist=== | ===The Jist=== | ||
Along with the other statins, Simvastatin works well and is quite safe. Depending upon the patient, Simvastatin can be the most effective statin at reducing LDL, but can also have dramatically reduced efficacy. Since Simvastatin is the most powerful HMGR inhibitor with an IC<sub>50</sub> of 66nM, this allows for decreased long-term exposure to the drug (lower AUC) and negates the short half life of Simvastatin compared to Atorvastatin and Rosuvastatin. While on patent it was one of the best selling drugs in the world. To maintain its market share after losing patent protection, Merck dramatically reduced the price of Zocor for insurance companies well below the price of existing statin generics, making the drug particularly attractive to US Health Insurers looking to reduce costs. <ref>http://timesofindia.indiatimes.com/business/india-business/Mercks-Zocor-price-cut-a-mixed-bag-for-drug-cos/articleshow/1690722.cms</ref> | |||
===References=== | ===References=== | ||
<references/> | <references/> | ||
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